Silica supported perchloric acid: an efficient catalyst for the synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones

SHORT REPORT

Silica supported perchloric acid: an efficient catalyst for the synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones

Li Qiang Wu^*; Yan Fang Wu; Chun Guang Yang; Li Min Yang; Li Juan Yang

School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China

ABSTRACT

The condensation of β-naphthol with aromatic aldehydes and 2-hydroxynaphthalene-1,4-dione in presence of silica supported perchloric acid under solvent-free media to afford the corresponding 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones in excellent yields and short reaction times is described. The reaction work-up is very simple and the catalyst can be easily separated from the reaction mixture and reused several times in subsequent reactions.

Keywords: dibenzo[a,i]xanthenes, β-naphthol, 2-hydroxynaphthalene-1,4-dione, silica supported perchloric acid, solvent-free

RESUMO

Este trabalho descreve a obtenção de 14-aril-14H-dibenzo[a,i]xanteno-8,13-dionas, com excelentes rendimentos e em um curto tempo de reação, a partir da reação de condensação do β-naftol com aldeídos aromáticos e 2-hidroxinaftaleno-1,4-dionas na presença de sílica suportada em ácido perclórico em um meio livre de solvente. A reação é muito simples e o catalisador pode ser separado facilmente da mistura reacional e, ainda, ser reutilizado por muitas vezes em reações subseqüentes.

Introduction

Xanthenes and benzoxanthenes have been reported to posses diverse biological and therapeutic properties such as antibacterial,¹ antiviral,² and anti-inflammatory activities,³ as well as photodynamic therapy⁴ and for antagonism of the paralyzing action of zoxazolamine.⁵ The other useful applications of this heterocycles are as dyes,⁶ fluorescent materials for visualization of biomolecules,⁷ and in laser technologies.⁸ Many procedures have been developed for the synthesis of xanthenes and benzoxanthenes, which include trapping of benzynes by phenols,⁹ cyclocondensation between 2-hydroxyaromatic aldehydes and 2-tetralone,¹⁰ cyclodehydrations,¹¹ and intramolecular phenyl carbonyl reaction of aldehydes with 5,5-dimethylcyclohexane-1,3-dione¹² or β-naphthol.¹³ Furthermore, the synthesis of benzoxanthenes and their related products include the reaction of β-naphthol with formamide,¹⁴ carbon monoxide,¹⁵ 2-naphthol-1-methanol,¹⁶ aldehydes and cyclic 1,3-dicarbonyl compounds.¹⁷

In recent years, the use of heterogeneous catalysts has received considerable interest in various disciplines including organic synthesis. They are advantageous over their homogeneous counterparts due to the prime advantage that in most of the cases the catalyst can be recovered easily and reused. Silica supported perchloric acid (HClO₄-SiO₂) has been used as an efficient heterogeneous catalyst for many organic transformations because of its low cost, ease of preparation, catalyst recycling, and ease of handling.¹⁸ We now report a simple and efficient route to synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones using HClO₄-SiO₂ as an efficient catalyst under solvent-free conditions (Scheme 1).

Results and Discussion

Initially, to optimize the amount of catalyst and the reaction temperature, the reaction of β-naphthol, benzaldehyde and 2-hydroxy-1,4-naphthoquinone was studied under solvent-free conditions in the presence of HClO₄-SiO₂ at different temperatures. The results were summarized in Table 1, and showed that the reaction using 5 mol % HClO₄-SiO₂ at 110 °C proceeded in highest yield.

Based on the optimized reaction conditions, several syntheses of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones from the condensation of β-naphthol, 2-hydroxynaphthalene-1,4-dione, and a wide range of aromatic aldehydes utilizing HClO₄-SiO₂ under solvent-free conditions at 110 °C were examined. All reactions were complete with in 1-2 h, as indicated in Table 2; in all cases the reactions afforded the desired products in excellent yields. When this reaction was carried out with aliphatic aldehyde such as butanal or pentanal, TLC and ¹H NMR spectra of the reaction mixture showed a combination of starting materials and numerous products, the yield of the expected product was very poor.

The reusability of the catalyst was checked by separating HClO₄-SiO₂ from the reaction mixture by simple filtration, washing with CHCl₃, and drying in a vaccum oven at 60 °C for 10 h prior to reuse in subsequent reactions. The recovered catalyst can be reused at least three additional times in subsequent reactions without significant loss in product yield (Table 3).

Although the detailed mechanism of the above reaction remains to be fully clarified, the formation of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones could be explained by a reaction sequence presented in Scheme 2. We proposed that the reaction proceeded via a reaction sequence of condensation, addition, cyclization and dehydration. First, the condensation of aldehyde (2) and β-naphthol (1) gave the intermediate ortho-quinone methide (5). The addition of 2-hydroxynaphthalene-1,4-dione (3) to (5) leading to the formation of (6), which on intermolecular cyclization gave rise to (7). In the last step, the intermediate product (7) undergoes dehydration to afford the desired product (4). In β-naphthol the electron density at the benzylic C-1 position (which is in conjugation with the aromatic ring) is higher than that at the C-3 position. Thus the regioselective formation of the ortho-quinone methide from this compound involving the C-1 and C-2 positions is favored. In simple phenolic compounds and a-naphthol (which are weaker nucleophiles compared to β-naphthol) the electron density at the ortho position of the hydroxyl group is not sufficient for the reaction of these compounds with the aldehydes leading to the formation of the corresponding ortho-quinone methides.

Conclusions

In conclusion, we have developed a simple and efficient protocol for the synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones using HClO₄-SiO₂ under solvent-free conditions. Short reaction times, simple work-up in isolation of the products in high yields with high purity, mild reaction conditions and recyclability of supported catalyst are features of this procedure.

Experimental

NMR spectra were determined on Bruker AV-400 spectrometer at room temperature using TMS as internal standard. Chemical shifts (δ) are given in ppm and coupling constants (J) in Hz. Mass spectra were recorded on a Finnigan LCQ Advantage mass spectrometer. Elemental analysis were performed by a Vario-III elemental analyzer. Melting points were determined on a XT-4 binocular microscope and were uncorrected. Commercially available reagents were used throughout without further purification unless otherwise stated.

Preparation of HClO₄-SiO₂ catalyst

HClO₄ (1.8 g, 12.5 mmol, as 70% aqueous solution) was added to a suspension of SiO₂ (230-400 mesh, 23.7 g) in Et₂O (70.0 mL). The mixture was concentrated and the residue was heated at 100 °C for 72 h under vacuum to furnish HClO₄-SiO₂ (0.5 mmol g⁻¹) as a free flowing powder (50 mg = 0.025 mmol of HClO₄).

General procedure for the preparation of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones

A mixture of β-naphthol (1 mmol), aldehyde (1 mmol), 2-hydroxynaphthalene-1,4-dione (1 mmol) and HClO₄‑SiO₂ (100 mg, 0.05 mmol) was heated at 110 °C for an appropriate time and monitored by TLC until the final conversion. After cooling, the reaction mixture was washed with CHCl₃ and filtered to recover the catalyst. Solvent was evaporated and the crude product puried by silica gel column chromatography using CHCl₃ as eluent to afford the pure product.

14-Phenyl-14H-dibenzo[a,i]xanthene-8,13-dione (4a): Yellow powder, mp 319-320 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.17 (d, 1H, J 7.6 Hz), 8.12 (d, 1H, J 7.6 Hz), 7.99 (d, 1H, J 8.4 Hz), 7.91-7.77 (m, 3H), 7.61-7.41 (m, 6H), 7.20 (t, 2H, J 8.0 Hz), 7.12-7.09 (m, 1H), 5.95 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.3, 157.2, 147.3, 143.1, 135.1, 131.9, 131.2, 131.0, 130.9, 130.0, 129.5, 129.4, 128.6, 127.5, 126.8, 125.5, 124.5, 123.8, 116.9, 116.8, 116.6, 35.2; MS (ESI): m/z 389 [M+H]⁺; Anal. Calc. for C₂₇H₁₆O₃: C, 83.49; H, 4.15. Found: C, 83.25; H, 4.12%.

14-(4-Chlorophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4b): Yellow powder, mp 305-306 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.16 (d, 1H, J 7.6 Hz), 8.13 (d, 1H, J 7.6 Hz), 7.92-7.77 (m, 4H), 7.62-7.44 (m, 4H), 7.34 (d, 2H, J 8.4 Hz), 7.15 (d, 2H, J 8.4 Hz), 5.90 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.2, 157.3, 147.2, 141.6, 135.2, 132.7, 131.9, 131.4, 130.8, 130.7, 130.0, 120.0, 129.8, 129.5, 128.7, 127.6, 125.7, 124.6, 123.6, 116.8, 116.3, 116.0, 34.6; MS (ESI): m/z 423 [M+H]⁺; Anal. Calc. for C₂₇H₁₅ClO₃: C, 76.69; H, 3.58. Found: C, 76.48; H, 3.62%.

14-(4-Methoxylphenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4c): Yellow powder, mp 279-280 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.16 (d, 1H, J 8.0 Hz), 8.12 (d, 1H, J 7.6 Hz), 7.98 (d, 1H, J 8.4 Hz), 7.89-7.76 (m, 4H), 7.60‑7.43 (m, 5H), 7.31 (d, 2H, J 8.4 Hz), 5.90 (s, 1H), 3.69 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.4, 158.3, 157.0, 147.2, 135.5, 135.1, 131.9, 131.2, 131.0, 130.0, 129.6, 129.4, 128.5, 127.4, 125.5, 124.5, 123.8, 117.1, 116.8, 113.9, 55.1, 34.3; MS (ESI): m/z 419 [M+H]⁺; Anal. Calc. for C₂₈H₁₈O₄: C, 80.37; H, 4.34. Found: C, 80.50; H, 4.27%.

14-(4-Methylphenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4d): Yellow powder; mp 255-256 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.16 (d, 1H, J 8.0 Hz), 8.11 (d, 1H, J 7.6 Hz), 7.99 (d, 1H, J 8.0 Hz), 7.89-7.76 (m, 3H), 7.60-7.42 (m, 4H), 7.29 (d, 2H, J 8.0 Hz), 7.00 (d, 2H, J 7.6 Hz), 5.90 (s, 1H), 2.21 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.3, 178.2, 157.1, 147.2, 140.3, 136.5, 135.1, 131.9, 131.2, 131.0, 130.9, 120.0, 129.4, 129.3, 129.2, 128.5, 128.4, 127.4, 125.5, 124.5, 123.8, 117.0, 116.8, 116.7, 34.7, 21.0; MS (ESI): m/z 403 [M+H]⁺; Anal. Calc. for C₂₈H₁₈O₃: C, 83.57; H, 4.51. Found: C, 83.49; H, 4.63%.

14-(4-Nitrophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4e): Yellow powder, mp 332-333 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.20 (d, 1H, J 7.6 Hz), 8.15 (d, 1H, J 7.6 Hz), 8.06 (d, 2H, J 8.8 Hz), 7.97-7.81 (m, 4H), 7.66-7.49 (m, 6H), 6.06 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.2, 178.0, 157.8, 150.0, 147.3, 146.7, 135.3, 132.0, 131.7, 130.7, 130.4, 130.3, 130.0, 129.6, 128.8, 127.9, 125.9, 124.8, 123.9, 123.3, 116.8, 115.4, 115.0, 35.3; MS (ESI): m/z 434 [M+H]⁺; Anal. Calc. for C₂₇H₁₅NO₅: C, 74.82; H, 3.49; N, 3.23. Found: C, 74.91; H, 3.38; N, 3.29%.

14-(3- Nitrophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4f): Yellow powder, mp 304-305 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.22 (d, 1H, J 8.0 Hz), 8.15 (d, 1H, J 8.0 Hz), 8.12 (s, 1H), 8.00-7.82 (m, 6H), 7.66-7.61 (m, 2H), 7.52-7.41 (m, 3H), 6.06 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.1, 178.0, 157.7, 148.6, 147.3, 145.1, 135.3, 135.1, 132.0, 131.7, 130.6, 130.4, 130.1, 129.6, 129.4, 128.9, 127.8, 125.9, 124.9, 123.3, 122.1, 117.0, 115.3, 115.2, 35.2; MS (ESI): m/z 434 [M+H]⁺; Anal. Calc. for C₂₇H₁₅NO₅: C, 74.82; H, 3.49; N, 3.23. Found: C, 74.76; H, 3.56; N, 3.25%.

14-(2,4-Dichlorophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4g): Yellow powder, mp 301-302 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.20 (d, 1H, J 8.4 Hz), 8.16-8.11 (m, 2H), 7.89-7.80 (m, 3H), 7.65-7.45 (m, 4H), 7.31-7.27 (m, 2H), 7.07-7.05 (m, 1H), 6.14 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.1, 157.6, 147.1, 139.2, 135.2, 134.0, 133.1, 132.6, 131.8, 131.5, 131.1, 130.6, 130.1, 130.0, 129.8, 129.5, 128.7, 127.7, 127.5, 125.7, 124.7, 123.7, 116.8, 33.2; MS (ESI): m/z 457 [M+H]⁺; Anal. Calc. for C₂₇H₁₄Cl₂O₃: C, 70.91; H, 3.09. Found: C, 70.82; H, 3.11%.

14-(3,4-Dichlorophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4h): Yellow powder, mp 260-261 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.19 (d, 1H, J 7.6 Hz), 8.16 (d, 1H, J 7.6 Hz), 7.95-7.82 (m, 4H), 7.65-7.43 (m, 5H), 7.31-7.30 (m, 2H), 5.92 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.2, 178.0, 157.6, 147.3, 143.2, 135.2, 132.7, 132.0, 131.6, 131.1, 130.7, 130.5, 130.4, 130.1, 129.6, 128.8, 128.2, 127.8, 125.8, 124.7, 123.4, 116.8, 115.6, 115.4, 34.6; MS (ESI): m/z 457 [M+H]⁺; Anal. Calc. for C₂₇H₁₄Cl₂O₃: C, 70.91; H, 3.09. Found: C, 70.95; H, 3.02%.

14-(2-Chlorophenyl)-14H-dibenzo[a,i]xanthene-8,13-dione (4i): Yellow powder, mp 281-282 °C; ¹H NMR (CDCl₃, 400 MHz) δ 8.25-8.22 (m, 2H), 8.14 (d, 1H, J 7.2 Hz), 7.89-7.83 (m, 3H), 7.65-7.29 (m, 6H), 7.08-7.04 (m, 2H), 6.22 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ 178.2, 178.1, 157.4, 147.1, 135.2, 133.3, 131.8, 131.4, 131.3, 130.8, 130.2, 130.1, 129.8, 129.4, 128.6, 128.2, 127.6, 127.1, 125.6, 124.7, 124.0, 116.8, 116.7, 115.6, 33.5; MS (ESI): m/z 423 [M+H]⁺; Anal. Calc. for C₂₇H₁₅ClO₃:C, 76.69; H, 3.58. Found: C, 76.79; H, 3.41%.

Supplementary Information

¹H NMR, ¹³C NMR spectra of compounds 4a-i are available free of charge at http://jbcs.sbq.org.br, as pdf file.

Acknowledgment

We are pleased to acknowledge the financial support from Xinxiang Medical University.

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Received: October 6, 2009

Web Release Date: March 11, 2010

Supplementary Information

Publication Dates

• Publication in this collection
  13 July 2010
• Date of issue
  2010

History

• Received
  06 Oct 2009
• Accepted
  11 Mar 2010